Up the junction? Exploiting knowledge-based development through supply chain and SME cluster interactions

Maximisation of Knowledge-Based Development (KBD) benefits requires effective dissemination and utilisation mechanisms to accompany the initial knowledge creation process. This work highlights the potential for interactions between Supply Chains (SCs) and Small and Medium sized Enterprise Clusters (SMECs), (including via ‘junction’ firms which are members of both networks), to facilitate such effective dissemination and utilisation of knowledge. In both these network types there are firms that readily utilise their relationships and ties for ongoing business success through innovation. The following chapter highlights the potential for such beneficial interactions between SCs and SMECs in key elements of KBD, particularly knowledge management, innovation and technology transfer. Because there has been little focus on the interactions between SCs and SMECs, particularly when firms simultaneously belong to both, this chapter examines the conduits through which information and knowledge can be transferred and utilised. It shows that each network type has its own distinct advantages in the types of information searched for and transferred amongst network member firms. Comparing and contrasting these advantages shows opportunities for both networks to leverage the knowledge sharing strengths of each other, through these ‘junctions’ to address their own weaknesses, allowing implications to be drawn concerning new ways of utilising relationships for mutual network gains.

Coordinated road-junction traffic control by dynamic programming

This paper presents a novel approach to road-traffic control for interconnected junctions. With a local fuzzy-logic controller (FLC) installed at each junction, a dynamic-programming (DP) technique is proposed to derive the green time for each phase in a traffic-light cycle. Coordination parameters from the adjacent junctions are also taken into consideration so that organized control is extended beyond a single junction. Instead of pursuing the absolute optimization of traffic delay, this study examines a practical approach to enable the simple implementation of coordination among junctions, while attempting to reduce delays, if possible. The simulation results show that the delay per vehicle can be substantially reduced, particularly when the traffic demand reaches the junction capacity. The implementation of this controller does not require complicated or demanding hardware, and such simplicity makes it a useful tool for offline studies or realtime control purposes.

Railway junction traffic control by heuristic methods

Traffic conflicts at railway junctions are very conmon, particularly on congested rail lines. While safe passage through the junction is well maintained by the signalling and interlocking systems, minimising the delays imposed on the trains by assigning the right-of-way sequence sensibly is a bonus to the quality of service. A deterministic method has been adopted to resolve the conflict, with the objective of minimising the total weighted delay. However, the computational demand remains significant. The applications of different heuristic methods to tackle this problem are reviewed and explored, elaborating their feasibility in various aspects and comparing their relative merits for further studies. As most heuristic methods do not guarantee a global optimum, this study focuses on the trade-off between computation time and optimality of the resolution.

Fuzzy logic traffic control at a road junction with time-varying flow rates

Fuzzy logic has been applied to control traffic at road junctions. A simple controller with one fixed rule-set is inadequate to minimise delays when traffic flow rate is time-varying and likely to span a wide range. To achieve better control, fuzzy rules adapted to the current traffic conditions are used.

Railway junction conflict resolution by genetic algorithm

In general, simple and traditional methods are applied to resolve traffic conflicts at railway junctions. They are, however, either inefficient or computationally demanding. A simple genetic algorithm is presented to enable a search for a near optimal resolution to be carried out while meeting the constraints on generation evolution and minimising the search time.

Hierarchical fuzzy logic traffic control at a road junction

Traffic control at road junctions is one of the major concerns in most metropolitan cities. Controllers of various approaches are available and the required control action is the effective green-time assigned to each traffic stream within a traffic-light cycle. The application of fuzzy logic provides the controller with the capability to handle uncertain natures of the system, such as drivers’ behaviour and random arrivals of vehicles. When turning traffic is allowed at the junction, the number of phases in the traffic-light cycle increases. The additional input variables inevitably complicate the controller and hence slow down the decision-making process, which is critical in this real-time control problem. In this paper, a hierarchical fuzzy logic controller is proposed to tackle this traffic control problem at a 2-way road junction with turning traffic. The two levels of fuzzy logic controllers devise the minimum effective green-time and fine-tune it respectively at each phase of a traffic-light cycle. The complexity of the controller at each level is reduced with smaller rule-set. The performance of this hierarchical controller is examined by comparison with a fixed-time controller under various traffic conditions. Substantial delay reduction has been achieved as a result and the performance and limitation of the controller will be discussed.

Railway junction conflict resolution by local search method

This study investigates the application of local search methods on the railway junction traffic conflict-resolution problem, with the objective of attaining a quick and reasonable solution. A procedure based on local search relies on finding a better solution than the current one by a search in the neighbourhood of the current one. The structure of neighbourhood is therefore very important to an efficient local search procedure. In this paper, the formulation of the structure of the solution, which is the right-of-way sequence assignment, is first described. Two new neighbourhood definitions are then proposed and the performance of the corresponding local search procedures is evaluated by simulation. It has been shown that they provide similar results but they can be used to handle different traffic conditions and system requirements.

Hierarchical fuzzy logic traffic control at a road junction using genetic algorithms

Traffic control at a road junction by a complex fuzzy logic controller is investigated. The increase in the complexity of junction means more number of input variables must be taken into account, which will increase the number of fuzzy rules in the system. A hierarchical fuzzy logic controller is introduced to reduce the number of rules. Besides, the increase in the complexity of the controller makes formulation of the fuzzy rules difficult. A genetic algorithm based off-line leaning algorithm is employed to generate the fuzzy rules. The learning algorithm uses constant flow-rates as training sets. The system is tested by both constant and time-varying flow-rates. Simulation results show that the proposed controller produces lower average delay than a fixed-time controller does under various traffic conditions.

Substrate recognition and catalysis by the Holliday junction resolving enzyme Hje

Two archaeal Holliday junction resolving enzymes, Holliday junction cleavage (Hjc) and Holliday junction endonuclease (Hje), have been characterized. Both are members of a nuclease superfamily that includes the type II restriction enzymes, although their DNA cleaving activity is highly specific for four-way junction structure and not nucleic acid sequence. Despite 28% sequence identity, Hje and Hjc cleave junctions with distinct cutting patterns—they cut different strands of a four-way junction, at different distances from the junction centre. We report the high-resolution crystal structure of Hje from Sulfolobus solfataricus. The structure provides a basis to explain the differences in substrate specificity of Hje and Hjc, which result from changes in dimer organization, and suggests a viral origin for the Hje gene. Structural and biochemical data support the modelling of an Hje:DNA junction complex, highlighting a flexible loop that interacts intimately with the junction centre. A highly conserved serine residue on this loop is shown to be essential for the enzyme's activity, suggesting a novel variation of the nuclease active site. The loop may act as a conformational switch, ensuring that the active site is completed only on binding a four-way junction, thus explaining the exquisite specificity of these enzymes.

Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses

Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the role of glucose in the pathogenesis of the disease has not been fully investigated. This study aimed to determine the endogenous insulin response to a quantity of glucose equivalent to that administered during a laminitis-inducing, euglycaemic, hyperinsulinaemic clamp, over 48. h in insulin-sensitive Standardbred racehorses. In addition, the study investigated whether glucose infusion, in the absence of exogenous insulin administration, would result in the development of clinical and histopathological evidence of laminitis. Glucose (50% dextrose) was infused intravenously at a rate of 0.68 mL/kg/h for 48. h in treated horses (n = 4) and control horses (n = 3) received a balanced electrolyte solution (0.68 mL/kg/h). Lamellar histology was examined at the conclusion of the experiment. Horses in the treatment group were insulin sensitive (M value 0.039 ± 0.0012. mmol/kg/min and M-to-I ratio (100×) 0.014 ± 0.002) as determined by an approximated hyperglycaemic clamp. Treated horses developed glycosuria, hyperglycaemia (10.7 ± 0.78. mmol/L) and hyperinsulinaemia (208 ± 26.1. μIU/mL), whereas control horses did not. None of the horses became lame as a consequence of the experiment but all of the treated horses developed histopathological evidence of laminitis in at least one foot. Combined with earlier studies, the results showed that laminitis may be induced by either insulin alone or a combination of insulin and glucose, but that it is unlikely to be due to a glucose overload mechanism. Based on the histopathological data, the potential threshold for insulin toxicity (i.e. laminitis) in horses may be at or below a serum concentration of ∼200. μIU/mL.

Managing intravenous medications in the non-hospital setting: An ethnographic investigation

Little published information exists about the issues involved in conducting complex intravenous medication therapy in patients' homes. An ethnographic study of a local hospital-in-the-home program in the Australian Capital Territory explored this phenomenon to identify those factors that had an impact on the use of medicine in the home environment. This article focuses on one of the three themes identified in the study-Clinical Practice. Within this theme, topics related to the organization and management of intravenous medications, geography and diversity of patient caseload, and communication in the practice setting are discussed. These findings have important implications for policy development and establishment of a research agenda for hospital-in-the-home services.

Differential pathologic variables and outcomes across the spectrum of adenocarcinoma of the esophagogastric junction

Background Adenocarcinoma of the esophagogastric junction (AEG) as described by Siewert et al. is classified as one entity in the latest (7th Edition) American Joint Cancer Committee/International Union Against Cancer (AJCC/UICC) manual, compared with the previous mix of esophageal and gastric staging systems. The origin of AEG tumors, esophageal or gastric, and their biology remain controversial, particularly for AEG type II (cardia) tumors. Methods We adapted a large prospective database (n = 520: 180 type I, 182 type II, 158 type III) to compare AEG tumors under the new TNM system Pathological variables associated with prognosis were compared (pT, pN, stage, differentiation, R status, lymphovascular invasion, perineural involvement, number of positive nodes, percent of positive nodes, and tumor length), as well as overall survival. Results Compared with AEG type I tumors, type II and type III tumors had significantly (p\0.05) more advanced pN stages, greater number and percentage of positive nodes, poorer differentiation, more radial margin involvement, and more perineural invasion. In AEG type I, 14/180 patients (8%) had[6 involved nodes (pN3), compared with 16 and 30% of patients classified type II and III, respectively. Median survival was significantly (p = 0.03) improved for type I patients (38 months) compared with those with tumors classified as type II (28 months) and type III (24 months). In multivariate analysis node positivity and pN staging but not AEG site had an impact on survival. Conclusions In this series AEG type I is associated with more favorable pathologic features and improved outcomes compared with AEG type II and III. This may reflect earlier diagnosis, but an alternative possibility, that type I may be a unique paradigm with more favorable biology, requires further study. © Société Internationale de Chirurgie 2010.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.